The current proposal will explore the role of cytokines in the response to group B streptococci (GBS) in vitro and in vivo in an experimental model. Studies are designed to examine the sequential appearance of tumor necrosis factor alpha. (TNFa), IL-1 beta (IL-1b), IL-6, and IL-8 following in vitro exposure of human mononuclear cells to GBS. The sequential appearance of these cytokines will also be assessed following GBS inoculation of neonatal rats. We will examine the role of fibronectin (FN) through the critical RGD sequence, in inducing or enhancing TNFa release by human mononuclear cells exposed to group B streptococci. The role of C5a as a co-factor along with GBS in causing cytokine release in vitro will also be explored. These studies will include experiments designed to determine if the GBS C5a-ase can affect C5a induction or enhancement of TNFa release. These studies should yield data that will help to explain the role of the proinflammatory cytokines in the pathogenesis of septic shock due to this most fulminant form of neonatal bacterial infection.